In general, basic drugs show low water-solubility as a compound in the free form per se under neutral or alkaline conditions. Accordingly, when a person who just finished eating or is suffering from anacidity takes such a drug, troubles including the delay of onset of efficacy and/or reduction of bioavailability (BA), etc. may be brought about because the drug ingested does not dissolve well.
In such cases, for the time being, drugs having a low solubility in water under neutral or alkaline conditions are converted into acid addition salts for the purpose of achieving rapid dissolution, improved bioavailability and early onset of efficacy thereof.
Besides, tablets or granules which quickly/rapidly disintegrate in the oral cavity have become available in these days so as to achieve early onset of action and easy ingestion. However, in these preparations, a drug begins to dissolve even in the oral cavity, and, therefore, even though said drug in the form of acid addition salt is highly water soluble, such preparations per se can hardly be administered to a patient as an intraorally rapidly disintegrating tablet or granule, if said drug has unpleasant taste.
There has been proposed a taste-masking technique, which, for example, comprising previously coated granules comprising acid addition salts of a drug with a polymer being soluble at low pH. For example, WO98/30209 discloses granulated preparation of sildenafil citrate coated with hydroxypropylmethyl cellulose and subsequently Eudragit® E100 (a gastric juice-soluble polymer). However, since said preparation uses a gastric juice-soluble polymer as a coating agent, the release rate and bioavailability of the drug would be unfavorably affected and the onset of efficacy be hampered when a person who just finished eating or is suffering from anacidity takes the preparation.
It is known that there are many drugs of which efficacy is required to be expressed immediately after administration. For example, for the purpose of improving quality of life (QOL), a cyclic GMP (cGMP)-specific phosphodiesterase (PDE) inhibitor, especially PDE 5 inhibitor, is used as a medicament for erectile dysfunction. Such medicament preferably exerts the efficacy immediately after taking the same so that the sexual response can be controlled on demand.
However, in the case of rapid-release tablets of sildenafil citrate (Viagra tablets), which is clinically used as a PDE 5 inhibitor, it has been reported that one should take the preparation about 1 hour in advance of the time when the efficacy is expected to be expressed (WO00/24383, page 2). Besides, it has also been known a “rapidly disintegrating tablet in oral cavity” prepared by a process comprising subjecting a mixture containing sildenafil citrate and a bondable disintegrant to wet granulation followed by compression molding (JP-A 10-298062 (1998)). However, said preparation fails to mask bitterness of a drug sufficiently and hence has not been manufactured for commercialization.